Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

ABSTRACT Objective: To compare alignment efficiency and root resorption between nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) archwires after complete alignment in mandibular anterior region. Methods: In this two-arm parallel single-blind randomized controlled trial, forty-four patients with Class I malocclusion with mandibular anterior crowding were recruited form orthodontic clinic of All India Institute of Medical Sciences (Jodhpur, India). Patients were randomly allocated into NiTi and CuNiTi groups, with a 1:1 allocation. Alignment was performed using 0.014-in, 0.016-in, 0.018-in, 0.019x0.025-in archwire sequence in the respective groups, which terminated in 0.019 x 0.025-in stainless-steel working archwire. The primary outcome was alignment efficiency, measured on study models from baseline (T0) to the first, second, third, fourth and fifth-month (T5). Secondary outcome was root resorption, measured from CBCT scans taken at T0 and T5. Mixed-factorial ANOVA was used to compare Little’s Irregularity Index (LII). For assessing the proportion of patients with complete alignment at the end of each month, Kaplan-Meier survival curve was built and time to treatment completion was compared between groups using log rank test. Paired t-test was used to assess external apical root resorption (EARR) within groups, whereas independent t-test was used to evaluate LII and EARR between the groups. Results: Twenty-two patients were recruited in each group. One patient was lost to follow-up in the CuNiTi group. No statistically significant differences were observed in alignment efficiency between the groups (p>0.05). Intergroup comparison revealed that the changes in root measurement in three-dimensions were not statistically significant (p>0.05), except for mandibular right central incisor, which showed increased resorption at root apex in NiTi group (p<0.01). Conclusion: The two alignment archwires showed similar rate of alignment at all time points. Root resorption measurement did not differ between the NiTi and CuNiTi groups, except for the mandibular right central incisor, which showed more resorption in NiTi group.


INTRODUCTION
Clinically effective treatment aims at balancing light, continuous forces and the restriction of potential damage to the tooth and periodontal structures. 1 In the first stage of orthodontic treatment, alignment archwires should have the property of delivering light continuous forces for a longer period of time.
Nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) alloys are common archwire choices to achieve ideal alignment of teeth. 2 Quintão et al. 3 stated that the smaller force deflection of superelastic NiTi archwires, when compared with stainless steel ones, makes the former more favorable for correction of crowding.However, despite the availability of various archwires, a careful selection should be made, due to the differences in expression of their properties in vivo. 1 A light continuous force is usually desired throughout the fixed orthodontic treatment.Dalaie et al. 4 have shown that there is no adverse effect of leveling and alignment on root length of immature teeth.However, heavy orthodontic forces may lead to potential side-effects like pain and root resorption.
According to Tripuwabhrut et al., 5 orthodontic forces represent a physical agent that is itself capable of inducing inflammatory reaction in the periodontium.Orthodontically induced external apical root resorption (EARR) is one of the most commonly seen iatrogenic damage of fixed orthodontic treatment, which is a result of inflammation caused by excessive forces.7][8] Cone beam computed tomography (CBCT) appears to be a better and reliable tool to assess root resorption with marked accuracy. 9It has been used to assess EARR after rapid maxillary expansion, 10,11 intrusion movements, 12,13 initial alignment and leveling, 7,14,15 and after complete orthodontic treatment. 16Patients with detectable root resorption during the first six-months of active treatment have been reported to have greater resorption in the following six-month period. 16,17[20][21][22][23][24] However, there is insufficient data to make clear recommendations regarding the superiority of any available archwire, in relation to their effectiveness and efficacy, due to the small number of robust in-vivo studies. 24A Cochrane review stated that more extensive studies are needed to formulate specific guidelines. 25The studies evaluating root resorption after the initial phase of alignment using CBCT have assessed changes in root length mainly in sagittal section.Comprehensive three-dimensional assessment of EARR in all sections after alignment and leveling has been rarely reported.The present study is probably the first to compare three-dimensional (sagittal, coronal and axial section) changes in root measurement using CBCT between NiTi and CuNiTi groups.The primary outcome of this study was to compare the alignment efficiency.Three-dimensional assessment of root resorption was the secondary outcome.The null hypothesis was that there would be no difference in alignment efficiency and EARR after complete alignment between NiTi and CuNiTi archwires.

TRIAL DESIGN
The study was an open-label, parallel-group and randomized clinical trial, with a 1:1 allocation ratio.No changes were made in methodology after trial commencement.
The CONSORT statement reporting guidelines were followed mandibular anterior crowding, based on the contact point displacement, were recruited for the study. 26The inclusion and exclusion criteria of the participants are shown in Table 1.

RANDOMIZATION, ALLOCATION CONCEALMENT AND BLINDING
Patients were randomly allocated into two groups using computer-generated variable block randomization scheme, in a specific software (Random Allocation Software 2.0, Microsoft Corporation, WA, USA).The allocation concealment was achieved using an opaque sealed envelope (sequentially numbered as per randomization scheme).Operator was handed over these envelopes by a person not involved in the trial.
The outcome assessor, participants and the statistician were blinded; however, the operator could not be blinded to the allocation groups.The information of the participants was anonymized using non-identifiable codes and removing identifying information.

OUTCOMES
To assess alignment efficiency, mandibular impressions were taken at the beginning of fixed orthodontic treatment and thereafter every month, up to five-months of treatment.CBCT scan of mandibular anterior region were obtained at pre-treatment and post-alignment stage.The scan was obtained using a using a CBCT unit (KODAK 9600 3D ® ; Carestream Health, Inc., Marne-la-Vallée, France), with reduced field of view (5x5cm) 27 and voxel size of 0.15mm, as suggested by Samandara et al. 9 , » Primary outcomes -Alignment efficiency was analyzed assessing the reduction in the Little's irregularity index (LII) 28 , to measure crowding of mandibular anterior region, on study models obtained at T0 to T5. Displacement of contact point as described in the index was measured with the help of a digital caliper with a sharpened fine edge to the nearest 0.01 mm (Standard Digital Caliper Series: EC16) on the study models. 19,29,30Alignment was considered complete when LII was  near zero and 0.019×0.025-instainless-steel working archwire was passive in the bracket slots (T5).
» Secondary outcomes -Changes in the root length and apical root dimensions were assessed for the four mandibular incisors at T0 and T5 in CBCT scans of mandibular anterior region, as per measurements described in Table 3 and Figure 2.

SAMPLE SIZE
Sample size was calculated based on the previous study by Serafim et al. 30 Assuming a proportion of 73% and 100% patients achieving complete alignment in the two groups, and population risk difference of 0.

Root length (mm)
The scan was adjusted along the long axis for the tooth to be measured, such that the horizontal reference line of software passes through cemento-enamel junction (CEJ).The length of the root was measured along the long axis of the tooth, passing from the most apical point of the root to the reference line perpendicularly.The root length measurements were made in sagittal and coronal sections for the four mandibular incisors (Fig 2A -B).

Apical root dimension (mm)
The root length was measured from CEJ to the apex, and marked 2mm short of apex using 'landmark' tool in the coronal section in pre-treatment scans (T0).Axial slice was viewed at this level and labio-lingual and mesio-distal dimensions were measured to determine apical root diameter.Post-alignment scans (T5) were evaluated at the same root level from CEJ in the coronal section as T0, for the apical root measurements (Fig 2C ).

PRIMARY OUTCOME
There was a significant improvement in LII after every month in NiTi and CuNiTi groups; however, the difference in LII with time was not significant (p>0.05) between the two groups (Tables 5 and 6).The log-rank test revealed no statistically significant difference between the two types of alignment archwires (p>0.05) in terms of survival function (Fig 3).No statistically significant difference (p>0.05) was present in both the groups, in terms of number of patients in which alignment was incomplete at the end of five months (Table 7).Values are presented as mean (SD), or n (%).SD = standard deviation, NiTi = nickel-titanium, CuNiTi = coppernickel-titanium, LII = Little's irregularity index, NS = non-significant.

SECONDARY OUTCOME
The intragroup comparison showed significant differences (p<0.05) in root length and apical root dimension (labio-lingual and mesio-distal measurements) in all four mandibular incisors in both groups (Table 8).However, the differences between the two groups were not statistically significant (p>0.05) for all measurements, except for the mandibular right central incisor, which showed significantly higher resorption in NiTi group for apical root dimension, both in mesio-distal and labio-lingual dimension (Table 9).

HARMS
No adverse events were reported during treatment, except a slight EARR that was within the limits of usual occurrence during orthodontic treatment.

ALIGNMENT EFFICIENCY
On evaluating alignment efficiency with both the archwires, LII scores approached zero after five-months with similar rate of alignment at each time-point.This shows that NiTi and CuNiTi were similar regarding their alignment efficiency to relieve moderate to severe crowding.Previous studies found no significant difference regarding alignment efficiency between CuNiTi and other NiTi archwires (conventional and superelastic). 20,21,31,32Riley and Bearn 33 conducted a systematic review and found inadequate evidence for determining the most effective archwire for alignment.In terms of alignment efficiency and sequence of aligning archwires, similar findings were reported by a meta-analysis by Papageorgiou et al. 24 A recent Cochrane review found no sufficient evidence to substantiate superiority of any archwire material for alignment and levelling. 25is review identified twelve studies, out of which only two studies compared conventional NiTi with CuNiTi, and none of them used rectangular archwires in the sequence -and therefore, may not contribute to greater evidence.The present study used conventional MBT bracket system, which was not used in both of these studies.The authors suggested a need of well-designed randomized control trial to evaluate the effectiveness of any archwire, due to presence of existing low quality of evidence. 25Therefore, all of the previous systematic Previous studies by Abdelrahman et al. 21and Pandis et al. 20 evaluated alignment efficiency using only a single round archwire for the entire duration of the study.In the former study, 0.014-in NiTi archwire was used and an impression was taken at every 2-week for 16-weeks, while in the latter 0.016-in NiTi archwire was evaluated monthly for six months without any further change in the archwire.We believe that evaluation of alignment at every 2-weeks may not offer any additional advantage, as a significant tooth movement is unlikely to occur in such a short period.Recall visits at three weeks or less may be insufficient for archwires to completely express their alignment efficiency.In the present study, the archwires were changed after every month, which is commonly accepted. 34Although the results of the present study are in agreement with previous studies, there is a lot of variation in evaluation periods (ranging between 2-weeks to 6-9 months) and the type and sequence of archwires used in the literature. 20,21,31,32e present study used both round and rectangular archwire sequences for complete alignment.Most studies 18,20,21,31,32 in the past included only round wires and very few reported the use of both round and rectangular wires in evaluation of alignment efficiency.

ROOT RESORPTION
The significance of assessing root resorption at the initial phase of the treatment is that the teeth that show EARR in first 6-months of appliance placement are likely to present greater resorption by the end of treatment. 17Wang et al. 25 suggested more randomized trials with sufficient duration, in which the benefits and possible disadvantages associated with different types of the archwires currently being used should be reported.In the past, periapical radiographs were commonly used to study root resorption; however, there have inaccuracies associated with it. 35,36Lund et al. 15 found a slanting type of root resorption in many teeth, which can only be evaluated in three-dimensional radiography.Alamadi et al. 36 in their study also found that two-dimensional radiographs, such as periapical radiographs and panoramic radiographs, underestimated root resorption, especially the slanting type of apical resorption, when compared to three-dimensional imaging methods.
For detection of root resorption, three-dimensional imaging is considered superior to conventional imaging methods.
The radiation exposure associated with CBCT scans may be considered a potential disadvantage for the patients; however, the newer CBCT techniques have presented reduced radiation exposure, compared to conventional machines. 37,38 Samandara et al., 9 a voxel size of less than 0.2-mm is considered accurate for evaluating root resorption; therefore, a voxel size of 0.15 mm was used for evaluating root resorption in the present study, which enabled visualization of small changes in root surface.
Sagittal and coronal slices of CBCT showed a significant EARR in all mandibular incisors post-alignment, irrespective of the archwire used, which is also supported by the results of previous studies. 16,21A recent randomized control trial, corroborating the present study, also did not find any significant difference in EARR in mandibular incisors while comparing superelastic NiTi and heat-activated NiTi archwires. 29In a study by Neves et al., 39 the incidence of EARR was reported to be higher in patients treated with premolar extraction, although the results were based on periapical radiographs and involved only maxillary incisors.
There were no statistically significant differences in labiolingual and mesiodistal dimension in axial section between the two groups, except for the mandibular right central incisor, in which a significantly higher EARR was reported in NiTi group, both labio-lingually and mesio-distally, which was quite an unusual finding.A possible explanation could be the higher uncontrolled tipping produced in this particular tooth with the NiTi archwires.A previous study reported similar findings, in which mandibular left central incisor showed significantly more EARR while comparing superelastic NiTi with multi-stranded stainless-steel archwires. 6This may suggest a greater tendency for EARR in the NiTi archwires with a longer treatment duration.In the present study, we assessed mandibular incisors, which are the most commonly affected teeth after maxillary incisors. 11Direct comparison with previous studies was difficult, as most of the studies evaluated root resorption using either different type of appliances, 40 different archwires and their sequences, 18,29 assessment time, 16,18,29 imaging software or type of imaging modality. 41,42Future studies can benefit

STRENGTHS AND LIMITATIONS
Every patient enrolled in this trial was followed-up for a period of five months, which gave adequate opportunity to evaluate alignment.Additionally, EARR was truly studied in all three-dimensions.One of the limitations of the current study was that the interventions could have been evaluated in non-extraction patients as well.At present, the available literature shows a lot of variation in three-dimensional assessment of root resorption; therefore, a standard method of assessment will facilitate meaningful comparisons associated with various appliances and treatment mechanotherapy.The results of the study cannot be generalized, as it was based on a single-center study.Since the limitations were fairly minor, without any discernible effect on the primary or secondary outcomes, the objectives of the study were achieved, with minimal impact from the above limitations.

CONCLUSIONS
The following conclusions were drawn from the study: 1. Alignment efficiency did not differ significantly between NiTi and CuNiTi groups.
2. There were no statistically significant differences in root resorption in all three-dimensions between the two groups, except for mandibular right central incisor, which showed increased resorption in root apical dimension in NiTi group, when compared to the CuNiTi group.

Bhatia 5 Dental
NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

Bhatia 6 Dental
NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

(
Fig 1).The recruitment of orthodontic patients was done at the post-graduate orthodontic clinic, Department of Dentistry, AIIMS (Jodhpur, India), between July 2018 and March 2020.Forty-four patients who fulfilled the inclusion criteria were invited to participate in the study.Patients having Angle's Class I malocclusion with moderate (4-6 mm) to severe (>6 mm) Bhatia NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial Dental Press J Orthod.2023;28(6):e2323177

Bhatia NK, 10 Dental
Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial standard recommended settings (voltage = 120kV; current = 8mA; scan time = 10s).The data was then imported into Dolphin imaging software (version 11.95, Dolphin Imaging & Management Solutions, Chatsworth, Calif).
baseline) Placement of fixed appliances and 0.014-in archwire T1 (At the end of first month) Removal of 0.014-in archwire and placement of 0.016-in archwire T2 (At the end of second month) Removal of 0.016-in archwire and placement of 0.018-in archwire T3 (At the end of third month) Removal of 0.018-in archwire and placement of 0.019 × 0.025-in archwire T4 (At the end of fourth month) Removal of 0.019×0.025-inarchwire and placement of working 0.019×0.025-instainless-steel archwire T5 (At the end of fifth month) Completion of the alignment phase

BhatiaDental
NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

Figure 3 : 18 Dental
Figure3: Kaplan-Meier survival curves for the two groups used in the study.The y-axis gives the proportion of patients achieving complete alignment at different time points ( months on x axis ).There is no separation during the evaluation period, indicating no significant difference between the groups.

Bhatia NK,
Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial 22 Dental Press J Orthod.2023;28(6):e2323177 reviews highlighted the requirement of a robust and well-designed randomized control trial to evaluate efficiency of various archwires.

Bhatia NK,
Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial 26 Dental Press J Orthod.2023;28(6):e2323177 from the uniformity in the method and timing of assessment of EARR.The results of the present study showed a significant root resorption observed in the alignment stage; therefore, a regular radiographic follow-up of the patients undergoing fixed orthodontic treatment is suggested.

Bhatia NK, 27 Dental
Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

Bhatia NK, 28 Dental
Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial

Table 2 :
Time period and archwire sequence used in the study.

Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial 11
Dental Press J Orthod.2023;28(6):e2323177

Table 3 :
Measurement used for evaluation of root resorption.

Bhatia NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial 13 Dental
Press J Orthod.2023;28(6):e2323177 INTERIM ANALYSES AND STOPPING GUIDELINES Not applicable.Normal distribution was assessed using Shapiro-Wilk tests.Descriptive statistics of means and standard deviations (SD) were calculated.Chi-square test/Fisher's Exact test was applied to compare baseline categorical data.Mixed factorial ANOVA was used to compare differences in the alignment between the groups with time interaction.Kaplan-Meier survival curve was built to illustrate proportion of patients who completed alignment at the end of each month.Log-rank test was used to compare time to treatment completion between groups.Paired t-test was used to assess EARR, before and after alignment within groups, and an independent t-test was used to evaluate the difference in LII and EARR between the groups.Bhatia NK, Chugh VK, Shankar SP, Vinay APR, Singh S, Moungkhom P, Sardana R -

Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial 14 Dental
Press J Orthod.2023;28(6):e2323177 the main examiner was excellent for LII and good to excellent for all measurements regarding EARR (Supplemental Table).Supplemental Table:Intraclass correlation coefficients for intra-examiner reproducibility and inter-examiner reliability.*P-valuerepresenting intra-examiner reproducibility.#P-value representing and inter-examiner reliability ** P-value < 0.05 is considered as significant; Intraclass correlation was analyzed using two-way mixed model, with absolute agreement.Bhatia NK,

Table 4 :
Baseline characteristics of participants in each study group.

Table 5 :
Mixed factorial ANOVA test for the difference between groups, according to the change in LII with time factor.

Table 6 :
Comparison of alignment efficiency using LII (mm) between NiTi and CuNiTi groups at different time intervals.

Table 7 :
Comparison of proportion of cases showing completion of alignment at T5, in each group.NiTi = nickel-titanium; CuNiTi = copper-nickel-titanium CI = Confidence Interval *p-value for comparison of percentage data by Fischer's Exact test CI-Mantel-Haenszel Common odds ratio.

Table 8 :
Comparison of linear changes in root length from T0-T5 (mm) in NiTi and Cu-NiTi groups.

Table 9 :
Comparison of linear changes in root length from T0-T5 (mm) between NiTi and CuNiTi groups.